Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis

Abstract

Background: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. Methods: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. Results: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii -derived butyrate were through the GPR (G protein-coupled receptor)-43. Conclusions: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.

Diabetic vascular diseases: molecular mechanisms and therapeutic strategies

“… 199 Orally administered Faecalibacterium exerts both anti-inflammatory and renoprotective effects on patients with CKD through butyrate-mediated G protein-coupled receptor-43 signaling. 200 Moreover, traditional Chinese medicine has also achieved considerable progress in DKD treatment, as a combination of Huangkui capsules and irbesartan was found to be more effective than either of the medications alone in reducing albumin-to-creatinine ratio in patients with DKD, 201 suggesting the potential role of Chinese medicine in future DKD therapy.…”

Gut microbiome and mycobiome in inflammatory bowel disease patients with Clostridioides difficile infection

“…We found a decreased proportion of Faecalibacterium and an increased proportion of Enterococcus in IBD patients with CDI compared with IBD-only. Faecalibacterium has been reported as a probiotic, which had anti-inflammatory potential via butyrate production and regulation of butyrate-mediated inflammatory pathways ( Roychowdhury et al., 2018 ; Zhou et al., 2018 ; Xu et al., 2020 ; Li et al., 2022a ). Depletion of Faecalibacterium has been observed in pediatric CD patients with CDI ( Hellmann et al., 2020 ).…”

Inflammatory Response: A Crucial Way for Gut Microbes to Regulate Cardiovascular Diseases

“…Most studies have confirmed the role of butyrate in regulating inflammatory responses. It was demonstrated that butyrate supplemented by Faecalibacterium ameliorated macrophage infiltration and reduced the levels of Mcpt1, IL-1β, and IL-6 in chronic kidney disease [ 38 ]. In alcoholic liver disease, butyrate was also found to significantly increase the plasma IL-10 concentration while decrease the level of plasma TNF-α [ 39 ], thus alleviating the progression of liver lesions.…”